TABLE 1

Experimental and calculated binding free energies (in kcal/mol) for the IRAP inhibitors

Calculated binding free energies are obtained with an optimized LIE model, with β=0.19 and γ=7.3 kcal/mol. Errors in calculated binding energies correspond to S.E.M. for replicate simulations

Ligand	Free		Bound		Enzyme K_i ± S.D.
Ligand					Enzyme K_i ± S.D.
					nM	kcal/mol	kcal/mol
HA08	−321.9 ± 2.5	−23.9 ± 0.2	−401.9 ± 0.7	−43.1 ± 0.2	3.3 ± 0.8	−11.6 ± 0.1	−11.6 ± 0.5
Ang IV	−357.8 ± 1.6	−37.9 ± 0.2	−417.9 ± 5.1	−66.6 ± 0.7	62.4 ± 17.5	−9.8 ± 0.2	−9.5 ± 1.0
Ang IV (γ-turn)	−346.0 ± 2.3	−35.9 ± 0.3	−409.6 ± 4.4	−64.6 ± 0.8	62.4 ± 17.5	−9.8 ± 0.2	−10.2 ± 1.0
HA09	−329.3 ± 1.4	−25.1 ± 0.1	−396.8 ± 1.3	−42.9 ± 0.4	242.0 ± 72.0	−9.0 ± 0.2	−8.9 ± 0.4